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J Biol Chem. 2015 Aug 14;290(33):20511-26. doi: 10.1074/jbc.M114.632257. Epub 2015 Jul 6.

Autophagy Protects against Colitis by the Maintenance of Normal Gut Microflora and Secretion of Mucus.

Author information

1
From the Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, the Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, and.
2
the Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, and.
3
the Department of Biochemistry, School of Medicine, Niigata University, Niigata 951-8510, Japan.
4
From the Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, the Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, and h-kawashima@hoshi.ac.jp.

Abstract

Genome-wide association studies of inflammatory bowel diseases identified susceptible loci containing an autophagy-related gene. However, the role of autophagy in the colon, a major affected area in inflammatory bowel diseases, is not clear. Here, we show that colonic epithelial cell-specific autophagy-related gene 7 (Atg7) conditional knock-out (cKO) mice showed exacerbation of experimental colitis with more abundant bacterial invasion into the colonic epithelium. Quantitative PCR analysis revealed that cKO mice had abnormal microflora with an increase of some genera. Consistently, expression of antimicrobial or antiparasitic peptides such as angiogenin-4, Relmβ, intelectin-1, and intelectin-2 as well as that of their inducer cytokines was significantly reduced in the cKO mice. Furthermore, secretion of colonic mucins that function as a mucosal barrier against bacterial invasion was also significantly diminished in cKO mice. Taken together, our results indicate that autophagy in colonic epithelial cells protects against colitis by the maintenance of normal gut microflora and secretion of mucus.

KEYWORDS:

antimicrobial peptide (AMP); autophagy; bacteria; colitis; intestinal epithelium; mucin

PMID:
26149685
PMCID:
PMC4536456
DOI:
10.1074/jbc.M114.632257
[Indexed for MEDLINE]
Free PMC Article

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